The production and application of stem cells useful in basic research, clinical research, and for cell-based therapies, such as for the generation of differentiated cells and/or tissues. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, provide a renewable source of replacement cells and tissues to treat diseases including, for example, Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, rheumatoid arthritis, amyotrophic lateral sclerosis, and so forth.
A variety of stem cells are known in different tissues of the body, and in many embodiments the tissue source of the stem cell does not limit the target application to which it will be applied. However, in other embodiments the stem cells are employed for a consonant tissue purpose. For example, adult bone marrow contains stem cells that replenish the haematopoietic system at a high turnover rate by generating cells of the myeloid and lymphoid lineages. Since bone marrow cells are accessible and readily available, the hypothesis arose that bone marrow may be a source of stem cells for tissues other than the haematopoietic system. The consequence of this rationale is that several laboratories are attempting to develop strategies to use bone marrow cells for brain cell replacement therapy. They have used ex vivo bone marrow cells, either unselected (Brazelton et al., 2000; Mezey et al., 2000; Makar et al., 2002; Hess et al., 2002) or a selected subpopulation (Bonilla et al., 2002; Caastro et al., 2002) or cells cultured from bone marrow (Azizi et al., 1998; Kpen et al., 1999; Woodbury et al., 2000; Kabos et al., 2002). When injected into recipient animals, bone marrow cells were found in the brain expressing neural markers in most cases. Previously, the neural myelin basic protein (MBP) gene was found to be expressed in bone marrow in vivo (Marty et al., 2002). This raised the possibility that some in vivo bone marrow cells express other neural genes.
WO 94/02593 concerns multipotent neural stem cells that are cultured in the absence of feeder cell layers. In specific embodiments liquid culture media is employed. In particular embodiments, however, the cells are cultured by contacting a substrate with an embryonic neural tube followed by contacting the cells with a second culture medium that permits self-regeneration and differentiation.
U.S. Pat. No. 5,830,651 is directed to methods of producing pre-oligodendroglial stem cells by culturing a neural cell in a vessel in a serum-containing basal media wherein a surface in the vessel allows attachment of the neural cell. In specific embodiments, the surface of the vessel is coated with a polybasic amino acid or an extracellular matrix molecule.
EP0455482 relates to human progenitor cells that are CD34+/CD38− and their use in bone marrow transplantation and gene therapy. Their isolation is accomplished by flow cytometry or magnetic bead cell separation, such as with using monoclonal antibodies.
The present invention satisfies a need in the art for culturing stem cells, including methods and compositions related thereto, such as application of the uniquely derived cells in a cell replacement therapy.